Palladium-103 (Pd-103) has a half-life of 16.97 days. It has many desirable properties for use as a therapeutic agent and is used, for example, in the treatment of cancers, such as prostate cancer. Its use with such seeds has been suggested as an alternative to I-125 (U.S. Pat. No. 3,351,049; U.S. Pat. No. 4,702,228; U.S. Pat. No. 5,405,309). In such applications, Pd-103 coated substrates, are subsequently coated or encapsulated by an inert material, and are used to produce small seeds, which are implanted directly into a tumour in order to provide irradiation for therapeutic treatment and inhibition of tumour growth.
The current production of Pd-103 involves neutron bombardment of a Pd-102 enriched (from about 50 to about 80%) substrate (U.S. Pat. No. 4,702,228), which is incorporated by reference), or transmutation of rhodium-103 by proton bombardment (U.S. Pat. No. 5,405,309; Harper et al 1961 both of which are incorporated by reference). The preparation of Pd-103 via transmutation of enriched Pd-102 target material is known to result in relatively low yields since only a small portion of the Pd-102 target is converted (U.S. Pat. No. 4,702,228; Harper 1961). The conditions for this reaction requires the use of a reactor to bombard the target material for 21 days, at a neutron flux of 4.times.10.sup.14 n/cm.sup.2 /s in order to provide an acceptable specific activity of Pd-103 (U.S. Pat. No. 4,702,228). U.S. Pat. No. 5,405,309, highlights other problems associated with producing Pd-103 from the transmutation of Pd-102 target materials which include:
the requirement for the use of high flux reactors; PA1 long exposure times of the target to the neutron beam; PA1 heterogeneous target materials comprising from 20-50% of other materials, including other Pd and non-Pd-isotopes, and therefore the product is of low specific activity; PA1 low radionuclidic purity; PA1 due to the combination of these above factors, a lack of predictability of the specific activity of the final product; PA1 the high cost of the Pd-102 starting material; and PA1 the low availability of Pd-102 starting material. PA1 difficulty of manufacturing robust Rhodium targets; PA1 dissolution resistance of Rhodium metal; and PA1 low production rates. PA1 i) providing a target material enriched with Pd isotopes comprising atomic masses equal to or greater than Pd-103; PA1 ii) applying the target material onto a target support; PA1 iii) irradiating the target material with protons or deuterons of sufficient incident energy and time to convert at least some of the Pd isotopes within the target material to Pd-103; and PA1 iv) purifying Pd from non-Pd components. PA1 i) adding a solvent to remove the target material from the target support to produce a target material solution; PA1 ii) adding at least one carrier, and precipitating the carrier from the target material solution; PA1 iii) removing the at least one carrier from the target material solution; PA1 v) reducing the Pd to the metallic state; and PA1 vi) collecting the Pd.
It is accepted within the art that methods that use bombardment involving (n,.gamma.) reactions (i.e. Pd-102 to Pd-103) are problematic due to quality issues associated with the final product. Pd-103 produced by this method is contaminated with impurities arising from other isotopes that are produced during the bombardment process. Furthermore, the use of Pd-102 for ion bombardment is also limited due to the high cost of Pd-102.
Second generation production of Pd-103 involves the use of Rhodium 103 targets, bombarded with cyclotron-produced protons at 10-17 MeV (U.S. Pat. No. 5,405,309; Harper et al 1961). This method suffers the following issues:
Other target materials used to produce Pd include high energy irradiation of silver (White et al 1962) or enriched Cadmium-106 materials. However these methods have limitations in their commercial application. For example the irradiation of silver is problematic since a non-compact cyclotron with high energy (70 to 90 MeV) is required. Also, Pd-100 is produced in this reaction which is undesirable, as Pd-100 decays to Rh-100 producing high .gamma. emission. Furthermore, target yields are limited since typical cyclotron beam currents of 100 .mu.A are used, and large amount of other isotopes are also formed resulting in subsequent radioactive waste issues of non-target isotope products. Irradiation of enriched Cadmium-106 is also problematic since a high energy (40 to 50 MeV) cyclotron is required, with target yields limited due to a 250 .mu.A beam current within the cyclotron. Furthermore, this method results in a low predicted makerate, and high cost and low availability of Cd-106.
Several reports have analysed inter-isotope conversions of Pd using (d,t) reactions. For example, Scholten et al (1980) examines reactions of Pd-102, 104,106,108 and 110 using deuteron beams of 50 MeV, or .sup.3 He at 70 MeV. Similarly, Cujec (1963) discloses the bombardment of the even numbered isotopes of Pd (Pd-104,106 and 108) using 15 MeV deuterons and an analysis of the Pd-104(d,t)Pd-103 reaction. Furthermore, Ames et al (1960) disclose reactions of Pd-102,104,106 and 108 bombarded with 11 MeV, below the (p,2n) threshold for Ag-103 production, and characterize the production of Ag-104. Ames et al also characterize the production of Ag-103 from Pd-104 with protons of 18.5 MeV energy (i.e. at the lower limit of the reaction) and the Pd104(p,2n)Ag103 reaction. Products produced within the above studies include Pd-103, however, no mention of product material recovery, optimizing make-rates of Pd-103, or providing for a commercially viable method for the production of Pd-103 is disclosed.
Another limitation in the above prior art methods for the production of Pd-103 products is related to difficulties in the separation of the product from the target support that is used for the products preparation. However, a method for optimizing the separation of target material from the target support is provided for by the method of this invention.
This invention is directed to a novel method for the production of Pd-103 that over comes the deficiencies of prior art methods. The method of this invention uses existing, commercially available, high capacity compact cyclotrons which are in common use for isotope production, it uses more cost effective, commercially available target materials compared to prior art methods, for example the method involving Pd-102. For example, the cost of enriched Pd-102 as a starting material is several fold that of a suitable enriched Pd-104 target. Furthermore, the production of Pd103 from Pd-104 should comprise as little Pd-102 as possible. The use of Pd-102 as a starting material, for cyclotron irradiation, is undesired since during irradiation both Pd-101 and Pd-100 are produced. These Pd isotopes decay to Rh-101 and Rh-100, and while Rh-101 is innocuous, Rh-100 is characterized problematic due to its .gamma. ray spectrum. Therefore, this invention also helps reduce the amount of Pd-101 and Pd-100 that is synthesised using associated prior art methods. Furthermore, the method of this invention uses a simple and effective chemical process for the complete recovery of the Pd-103, and produces large batches of Pd-103 of high radionuclidic purity and of acceptable specific activity. As a result, the method of this invention provides for the commercially feasible production of Pd-103.